Project Summary The Alliance of Genome Resources (the Alliance) is a ?knowledge commons? for expertly curated genomic data and annotations provided by model organism databases (MODs) and the Gene Ontology Consortium (GOC). Our mission is to facilitate the use of model organisms to understand human biology and disease. The Alliance is organized as two interconnected functional units: Alliance Central and Alliance Knowledge Centers. Alliance Central is responsible for development and maintenance of the software platform and shared modular infrastructure and for the coordination of data harmonization activities across the Knowledge Centers. Alliance Knowledge Centers such as the MODs and the GOC are responsible for expert curation and for submission of data to Alliance Central using common data formats. Knowledge Centers also are responsible for organism- specific user support activities, resources, and user access to data not yet supported by Alliance Central. This U24 application seeks support for the activities of Alliance Central. The proposal reflects a new and transformational approach to modernizing the MOD/GOC ecosystem, increasing the impact and utility of essential community genome resources, and optimizing operational efficiencies for knowledgebases. The aims build on the significant accomplishments we achieved as a consortium since we launched the Alliance in 2016, including: a common management and governance structure, Working Groups, multiple channels for communications among consortium members, infrastructure for coordinated software development and version control, data sharing with the NIH Data Commons Pilot initiative, the development of a common set of orthologs, the release of the Alliance web site and APIs, and successful development of software components that have been adopted by both Alliance members and external resources. Our focus for Specific Aim 1 will be on implementing a shared platform for ingesting, storing, and harmonizing data for MODs. We will continue our long-standing commitment to data management practices that align with FAIR principles. In Specific Aim 2 we describe our plans to implement common methods, including well-documented APIs, for access to model organism data and annotations. The deliverables for this aim will foster widespread adoption and use of Alliance data and resources for the development of new applications for biological discovery and translational research. In Specific Aim 3 we describe our plans to implement a framework to support the development and deployment of software applications, workflows, and analysis tools that use model organism data and annotations. The enhanced functionality for comparative genomics fostered by these innovations will empower the biomedical research community to leverage knowledge across multiple organisms for hypothesis generation and pattern discovery. Finally, in Specific Aim 4 we describe the management and organization of the Alliance as well as the planned activities of our centralized user support helpdesk.